Yoshiaki Sugiura

Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma

Angiogenesis is essential for solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator in vivo. Conversely, there have been few studies of the association between angiogenic factor expression and angiogenesis in esophageal carcinoma. The authors examined VEGF expression and microvessel density in esophageal squamous cell carcinomas to clarify the association of VEGF expression with the clinicopathologic features of the disease.

The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma.

Objectives: Recent studies have shown that some growth factor receptors with tyrosine kinase activity, eg, the epidermal growth factor receptor (EGFr) and the c-erbB-2 (HER-2) oncoprotein, are associated with aggressive biologic behavior of various cancer cell types. We examined the clinicopathological significance of the expression and localization of EGFr and HER-2 in both invasive and intraductal components of ductal adenocarcinomas of the pancreas. Methods: Tissue samples from 76 archival cases of pancreatic ductal adenocarcinoma were immunohistochemically analyzed for both membrane and cytoplasmic overexpression of EGFr and HER-2 oncoprotein. The rate of incidence between the invasive and intraductal components was analyzed and then their correlation with tumor differentiation and patient prognosis was analyzed. Results: Cytoplasmic EGFr overexpression was more frequent in invasive components (47 of 76, 62%) than in intraductal components (19 of 76, 25%), while membrane EGFr overexpression was more frequent in intraductal components (41 of 76, 54%) than in invasive components (11 of 76, 14%). The membrane HER-2 overexpression was also more frequent in intraductal components (15 of 76, 20%) than in invasive components (2 of 76, 3%), but the incidence of cytoplasmic HER-2 overexpression did not differ between intraductal components (12 of 76, 16%) and invasive components (8 of 76, 11%). The cytoplasmic EGFr overexpression in invasive components was more frequent in grade 3 group (32 of 33, 97%) than in grade 2 (15 of 32, 47%) and grade 1 groups (0 of 10, 0%) (P < 0.001). Patients with adenocarcinoma with cytoplasmic EGFr overexpression showed shorter overall survival than those with adenocarcinoma without cytoplasmic EGFr overexpression (P = 0.02). Conclusion: It is suggested that the cytoplasmic overexpression of EGFr plays a significant role in the progression of pancreatic ductal adenocarcinoma, especially in the invasion and acquisition of aggressive clinical behavior. Both membrane and cytoplasmic expression of HER-2 showed no significant correlation between tumor differentiation and poor survival.

Beneficial Effects of Immediate Enteral Nutrition After Esophageal Cancer Surgery

Abstract This study was conducted to determine the effects of immediate enteral nutrition (EN) on nutritional status, immunological competence, and the suppression of excessive inflammatory responses in patients following esophageal cancer surgery. Twenty-four patients who underwent the same elective operation for thoracic esophageal carcinoma were randomized into an immediate enteral nutrition (IEN) group who received EN from postoperative day (POD) 1 and a parenteral nutrition (PAN) group. Both groups received comparable volumes and calories on the same POD. Laboratory studies were carried out preoperatively and on PODs 1–7. Other nutritional and immunological assessments were repeated on PODs 1 and 7. Plasma concentrations of nitrate and nitrite were also measured. All of the patients in the IEN group tolerated enteral feeding well. There were no significant differences in the results of nutritional assessments, lymphocyte function, or plasma nitrate and nitrite levels between the two groups. The IEN group showed a significantly earlier recovery of the total lymphocyte count. The serum levels of total bilirubin and C-reactive protein were significantly attenuated in the IEN group. These results indicate that immediate EN may have beneficial effects on immunological competence and the suppression of excessive inflammatory responses in patients following esophagectomy. Patients undergoing radical esophageal surgery who are subjected to severe surgical stress might benefit the most from early EN.

Expression of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma

Hypoxia‐inducible factor‐1 (HIF‐1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF‐1α, a subunit of HIF‐1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF‐1α expression in esophageal squamous cell carcinoma. In 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF‐1α protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF‐1α messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase‐polymerase chain reaction [RT‐PCR]). A positive HIF‐1α protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the ‘high score’ group for HIF‐1α protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF‐1α protein was found to have a significant effect on disease‐free survival rate in our univariate analysis, but no effect on overall survival rate. In RT‐PCR, HIF‐1α mRNA scores correlated significantly with scores for HIF‐1α protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF‐1α protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma. (Cancer Sci 2005; 96: 176–182)

Potential crosstalk between insulin-like growth factor receptor type 1 and epidermal growth factor receptor in progression and metastasis of pancreatic cancer

The insulin-like growth factor receptor type 1 (IGF1R) and epidermal growth factor receptor (EGFR) are reportedly overexpressed in pancreatic cancer. However, the correlation between activated EGFR and IGF1R and their clinicopathological implications still remain unclear. The cellular localization and overexpression of IGF1R and EGFR were investigated immunohistochemically in primary invasive ductal pancreatic carcinomas obtained from 74 patients who underwent radical surgical resection. We also compared the status of IGF1R and EGFR overexpression between primary tumors and hepatic metastatic tumors obtained from 44 autopsied patients. Among the 74 surgically resected primary tumors, cytoplasm- and membrane-dominant EGFR overexpression was detected in 22 (30%) and 7 (9%), respectively, whereas cytoplasm- and membrane-dominant IGF1R overexpression was detected in 8 (11%) and 28 (38%), respectively. Membrane-dominant EGFR and cytoplasm-dominant IGF1R were more frequent in lower-grade tumors and correlated with favorable prognosis, whereas cytoplasm-dominant EGFR and membrane-dominant IGF1R were more frequent in higher-grade tumors and correlated with poor prognosis. In 36 autopsy specimens of pancreatic tumor with concurrent overexpression of IGF1R and EGFR, there was an inverse correlation between the IGF1R and EGFR localization patterns (P=0.001). In the hepatic metastatic tumors obtained by autopsy, the incidences of both IGF1R and EGFR overexpression were much higher than in the surgically resected primary tumors. More than half of the autopsy cases consistently showed membrane-dominant EGFR expression in both the primary tumor and hepatic metastases, whereas IGF1R expression showed considerable variation. Crosstalk between differently localized IGF1R and EGFR might play a role in determining the biological aggressiveness of pancreatic cancer, although their cellular localization may often alter during the process of metastasis.

The effects of immediate enteral feeding with a formula containing high levels of ω-3 fatty acids in patients after surgery for esophageal cancer

BACKGROUND We investigated whether supplementation of enteral nutrition (EN) with ω-3 polyunsaturated acids (PUFAs) affected platelet aggregation, coagulation activity, and inflammatory response in the early stages after esophageal cancer surgery. METHODS Twenty-eight patients with esophageal cancer who underwent the same surgical procedure were selected for this study. All patients received EN, which was started immediately after the operation and was increased to a maximum volume of 1500 ml/day by the third postoperative day (POD). Eleven patients received a conventional EN formula (Ensure Liquid), while the remaining 17 patients received a different formula rich in ω-3 PUFAs (Racol [RAC]). Several markers of coagulation and fibrinolysis were determined in POD 2, while the concentrations of interleukin (IL)-6, IL-8, 6-keto-PGF1α and thromboxane B2 were determined on PODs 1, 3, and 5. RESULTS A total of 27 patients completed the study, 11 in the Ensure Liquid group and 16 in the RAC group. Administration of RAC significantly inhibited the postoperative decrease in platelet count. The level of D-dimer was attenuated significantly in the RAC group. Plasma IL-8 levels were decreased significantly in the RAC group on PODs 1 and 3. The anti-inflammatory effects of ω-3 PUFAs were confirmed by the clinical findings of lower body temperature. The plasma concentration of 6-keto-PFG1α also tended to decrease in the RAC group with a significant difference on POD 5. CONCLUSIONS Early EN with a large amount of ω-3 PUFAs in reduced platelet aggregation, coagulation activity, and cytokine production. All these effects would be expected to be beneficial in patients following esophageal cancer surgery. The clinical significance of the changes in eicosanoid production remains to be established.

Localized malignant peritoneal mesothelioma containing rhabdoid cells

A case Is presented of localized malignant peritoneal mesothelioma appearing as a liver neoplasm. The patient underwent tumor resection but developed a recurrent growth and died 10 months after the Initial surgery. The primary tumor showed sarcomatous features with rhabdoid cells. Examination revealed the presence of hyaluronic acid, co‐Immunoreactivlty for cytokeratln epithelial membrane antigen and vlmentln, cellular contacts with small desmosomes, and intracytoplasmic lumina. These findings supported the mesothelial nature of this tumor. The recurrent tumor was composed of predominantly tubulopaplllary proliferation. It was concluded that the present tumor was a localized malignant mesothelioma of a blphasic type showing a predominantly sarcomatous component in the primary tumor.

High-level Skp2 expression in pancreatic ductal adenocarcinoma: correlation with the extent of lymph node metastasis, higher histological grade, and poorer patient outcome.

Objectives: Recent studies have shown that overexpression of S-phase kinase-associated protein 2 (Skp2) occurs in many cancers at an advanced stage. We examined the clinicopathologic significance and prognostic implication of Skp2 expression in pancreatic invasive ductal carcinoma. Methods: Tissue samples from 46 pancreatic carcinomas were examined immunohistochemically for Skp2. The proportion of constituent tumor cells with Skp2 expression was analyzed and classified as high-level nuclear expression when more than 20% of the cancer cells were positive, or low-level nuclear expression otherwise. Results: High-level Skp2 overexpression was detected in 13 (28.3%) of the 46 tumors. The incidence of high-level Skp2 was correlated with higher histological grade (P = 0.0056), the extent of lymph node metastasis (P = 0.0086), the level of lymphatic permeation (P = 0.0024), and poorer patient outcome (P = 0.0189). Multivariate analysis showed that high-level Skp2 expression was an independent predictor of overall patient survival (P = 0.0140). Conclusions: It is suggested that examination of Skp2 expression might be clinically useful for prognostication in patients with pancreatic carcinoma and that Skp2 protein might be a novel therapeutic molecular target.

The hypertrophic uncinate process of the pancreas wrapping the superior mesenteric vein and artery —A case report—

The hypertrophic uncinate process of the pancreas wrapping the superior mesenteric vein and artery was discovered during surgery on a patient with nodular chronic pancreatitis. Such a rare anomaly has never been noted in the English literature so far as we have been able to find. This malformation of the pancreatic uncinate process was considered to be due to excess fusion between the ventral and dorsal pancreatic anlages during embryonic stage.

Adenoid cystic carcinoma of the esophagus: Report of a case and review of the Japanese literature

We report herein the case of a 79-year-old man with adenoid cystic carcinoma (ACC) of the esophagus. The tumor had a polypoid appearance and was covered by thin esophageal mucosa. As the biopsy specimens suggested a diagnosis of poorly differentiated adenocarcinoma, the patient underwent subtotal esophagectomy with reconstruction of the gastric tube via the posterior mediastinum. Histologically, the carcinoma contained basaloid cells, cribriform foci, and a certain amount of eosinophilic hyaline substance. Some of the basaloid cells were stained immunohistochemically for keratin, muscle actin, and S-100 protein, a pattern which was identical to the pattern of immunoreactivity of the myoepithelium. We reviewed 36 other cases of ACC of the esophagus reported in Japan, with special reference to the criteria for histological diagnosis.